Tuesday, April 1, 2008

The heart of the matter

Yesterday, a country-wide attack occurred by the medical establishment against the makers of Zetia and Vytorin. These are two newer (and more expensive) cholesterol lowering medications.
A sample news article appears here, in the New York Times.
A brief analysis of the article in The New England Journal of Medicine, (article here) notes that there is failure to separate statistically between the new medications (specifically ezetimibe- found in both Zetia and Vytorin) and the older cholersterol lowering medications, known as statins (simvastatin, specifically, for this study). The ENHANCE study measured the lowereing of LDL ("bad" cholesterol) and the thickness of the intima-media of the femoral and carotid arteries (a way of noting how much plaque is building up in the actual arteries). The latter is designed to measure the amount of atherosclerosis, and thus if the drugs are likely to prevent heart disease. On LDL lowering performance, ezetimibe has shown consistent significance at lowering LDL's better than statins; this was also seen in the ENHANCE study. However, no statistical difference was noted in the intima-media thickness (IMT).
So we again have a study that fails to separate (See previous posts on statistics and separation). This evidince is a bit more solid insofar that the drug makers themselves are sponsoring this study, and that there is an upward trend in thickness noted in the data of the newer drugs. Clearly there would be difficulty in declaring any improvement regarding heart disease from the newer medications, as none to date can be shown, and from the IMT results. But let's note just a few points:

1. The older medication showed no difference in IMT either, yet these medications have been shown to reduce heart disease.
2. Ezetimibe does show consistently and significantly lower levels of cholesterol
3. Long term outcome studies on heart disease have not been finished with the newer medicinces.

However, such points do not stop the mainstream media from finding all to willing physicians to get on the TV, radio, and news to declare the absolute failure of these newer products.
I woke up yesterday to hearing a cardiologist on a morning TV program saying "You can prescribe these medications; they just don't work." A similar statement is noted in the NYT article, where Dr. Krumholz recommends going back to statins, because "they work." Well, perhaps.... but not any better than the newer medication if we are to believe the results of the ENHANCE study.

What the ENHANCE study shows, is that we do not understand the mechanisms and correlations between cholesterol and heart disease, and that we need to wait to consider outcome data, before any declaration of what does and doesn't work in prevention of heart disease. In the meanwhile, the newer medications should be considered as part of the ongoing armament to lowering cholesterol. The recommendations for treatment of Familial Hypercholesterolemia have never been to use the newer medications first, so continuing to follow these guidelines and start with more traditional treatment is currently prudent.

Yes, newer is not always better- but remember that statins were the new, expensive drugs once too.


BB-Idaho said...

Well before the study results, I tried Vytorin. But it excacerbated my arthritis and my physician returned me to Lipitor.
Us patients are not experts in pharmacology, but we know a stiff neck when we get one....

Doc said...

Absolutely right. And you were tried first on the older statin, which was appropriate. Some folks do not find the statins to be favorable to their GI system. I also have seem a number of patients with worsening memory on statins. (A particular difficulty for most of the patients I treat.)
I have no horse in that race, as I do not use any of these medications in my specialty. I do like science to be consistent, and not twisted to findings for political, sensational, or economic benefits.
The advertising of newer medications as being panaceas is equally immoral. I often amazed and saddened at the bias placed by trainees towards specific medications- usually those that are newest, and heavily promoted.
Thanks for the comment, and always be proactive with your physician. One of these days, I'll cover the study about the limited amounts of time and listening with patients that we are doing in the profession.